This program will continue to seek a better understanding of the mechanisms by which antitumor drugs inhibit growth of malignant neoplasms to improve their use clinically. We are examining the mechanism by which N,N-dialkyltriazenes produce their selective antitumor action. We shall investigate the role of demethylation of these compounds in their activation to the carcinostatic metabolite. The mechanism for the synergy between thioguanine and nitrogen mustard will be further explored to understand the increased antitumor effectiveness of the drug combination. The interrelationship will be studied between thymidylate synthetase and concentrations of fluorodeoxyuridylate and of deoxyuridylate during inhibition and recovery of DNA synthesis in L1210 tumor, GI mucosa and bone marrow in mice. The pharmacokinetics of stilphosterol and diethylstilbestrol will be investigated in dog prostate and prostatic tumor patients. The protective effect of forced diuresis on kidney toxicity from cis diammine platinum will be evaluated.